One necessary step in atherogenesis is the proliferation of smooth muscle cells (SMC) in the intima of the artery wall. The triggering mechanism for this phenomenon is not known. The overall objective of this proposal is to establish the role of endothelial-derived ad platelet-derived factors in the growth control of both arterial SMC and arterial endothelial cells (AEC). Three interrelated hypotheses will be tested by the proposed experiments. The first is that endothelial products, including the endothelial-derived growth factor (EDGF) and a platelet-derived growth of actor (PDGF) binding competitor, play a critical role in the proliferative response of vascular SMC both in vitro and in vivo. The second is that the in vivo production of these endothelial-derived factors is regulated by conditions and molecules which mimic an in vivo injury state of te endothelium. Thirdly, it is proposed that endothelial growth control itself is governed by endothelial-derived factors. The above hypotheses will be tested by employing bovine and swine arterial cells in culture to pursue the following goals: (i) the purification and detailed physical characterization of the endothelial-derived growthf actor (EDGF) from bovine AEC conditioned medium, (ii) the identification of EDGF cell surface receptors on vascular SMC, and the preparation of EDGF antiserum for in vivo identification ad localization of EDGF, (iii) the identification of factors or conditions which regulate the production of EDGF by AEC, (iv) the characterization of a factor in EDGF preparations that competes for binding of the platelet-derived growth factor (PDGF) to its cell surface receptor, and (v) the identification of latent high affinity receptors to EDGF or PDGF on the surface of AEC. The proposed research should shed some light on the role of cell-cell communication in the growth control of vascular cells, and help to elucidate the molecular mechanism of one step in atherogenesis.